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. 2025 Jun 28;52(1):649.
doi: 10.1007/s11033-025-10738-2.

The rs3757385 polymorphism increases IRF5 expression and systemic nitric oxide metabolites, protecting urothelial bladder cancer patients from recurrence

Ariane P Souza  1 , Isabely M Silva  1 , Beatriz G L Vacario  1 , Alexsandro Koike  2 , Rafael G Paz  3 , Carolina Coradi  3 , Emily M S Wrzesinski  3 , Guilherme L Trigo  4 , Andrea N C Simão  4 , Marcell A B Lozovoy  4 , Roberta L Guembarovski  1 , Carolina Panis  3 , Juliana Mara Serpeloni  5
Affiliations

The rs3757385 polymorphism increases IRF5 expression and systemic nitric oxide metabolites, protecting urothelial bladder cancer patients from recurrence

Ariane P Souza et al. Mol Biol Rep. .

Abstract

Background: Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide. It is essential to investigate factors that may affect susceptibility and determine the prognosis of UBC. IRF5 is an interferon regulatory factor that modulates cellular differentiation during immune responses and oncogenesis.

Methods and results: The frequency of the rs3757385 (T > G) variant in IRF5 was evaluated in 295 patients with UBC and 295 individuals without neoplasia in a Brazilian population. Nitric oxide metabolites (NOx) systemic levels and IRF5 expression in normal and tumoral bladder tissues were also evaluated, as was the interaction between these parameters and prognostic indicators. Bioinformatics analyses compared gene expression patterns with TCGA data. The polymorphism was not associated with susceptibility to UBC. The mutated allele (G) was associated with a decrease in the relapses in the genotypic (OR = 0.205) and dominant (OR = 0.380) models. Hypertensive individuals with TG (genotypic, OR = 0.079) or TG + GG (dominant model, OR = 0.184) had fewer muscle-invasive tumors. Polymorphism did not alter the plasmatic NOx levels. Higher IRF5 expression was observed in patients with at least one G allele, males, smokers, and alcoholics. Directly, NOx was not associated with the prognostic parameters; however, individuals with the G allele and high NOx levels showed protection against relapses.

Conclusion: Our study highlights the association between rs3757385 (G allele) and high plasmatic NOx levels as good prognostic factors in UBC.

Keywords: Inflammation; Interferon; Nitric oxide metabolites; Single nucleotide variant; Urothelial cancer.

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Conflict of interest statement

Declarations. Ethical approval: This study was conducted according to the principles of the Declaration of Helsinki and approved by the Institutional Research Ethics Committees of the University of Londrina, Paraná, Brazil (CAAE: 47092521.2.0000.5231). All invited individuals were informed in detail about the research and signed the informed consent form. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The study participants were informed about the present research, and written informed consent was obtained from them before their enrollment. Furthermore, all authors and co-authors participated in and contributed sufficiently to the study, and all agreed to the submission. The responsible authorities approved the manuscript in which the work was conducted. The authors also agree that, if accepted, the manuscript will not be published elsewhere in the same form, neither in the same nor in any other language, without the consent of the Editor of Molecular Biology Reports. Competing interests: The authors declare no competing interests.

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